Metabolite Damage and Damage Control in a Minimal Genome

Haas, Drago; Thamm, Antje M.; Sun, Jiayi; Huang, Lili; Sun, Lijie; Beaudoin, Guillaume W.; Wise, Kim S.; Lerma-Ortiz, Claudia; Bruner, Steven D.; Breuer, Marian; Luthey-Schulten, Zaida; Lin, Jiusheng; Wilson, Mark A.; Brown, Greg; Yakunin, Alexander F.; Kurilyak, Inna; Folz, Jacob; Fiehn, Oliver; Glass, John I.; Hanson, Andrew D.; Henry, Christopher S.; de Crécy-Lagard, Valérie

doi:10.1128/mbio.01630-22

Title: Metabolite Damage and Damage Control in a Minimal Genome

Journal Article · 11 July 2022 · mBio (Online)

DOI: https://doi.org/10.1128/mbio.01630-22 · OSTI ID:1889733

Haas, Drago ^[1]; Thamm, Antje M. ^[1]; Sun, Jiayi ^[1]; Huang, Lili ^[1]; Sun, Lijie ^[2]; Beaudoin, Guillaume W. ^[1]; Wise, Kim S. ^[2]; Lerma-Ortiz, Claudia ^[1]; Bruner, Steven D. ^[1]; Breuer, Marian ^[3]; Luthey-Schulten, Zaida ^[4]; Lin, Jiusheng ^[5]; Wilson, Mark A. ^[5]; Brown, Greg ^[6]; Yakunin, Alexander F. ^[7]; Kurilyak, Inna ^[8]; Folz, Jacob ^[8]; Fiehn, Oliver ^[8]; Glass, John I. ^[8]; Hanson, Andrew D. ^[1] more »

University of Florida, Gainesville, FL (United States)
J. Craig Venter Institute, La Jolla, CA (United States)
Maastricht University (Netherlands)
University of Illinois at Urbana-Champaign, IL (United States)
University of Nebraska, Lincoln, NE (United States)
Uniersity of Toronto, ON (Canada); Bangor University (United Kingdom)
University of Toronto, ON (Canada)
University of California, Davis, CA (United States)
Argonne National Lab. (ANL), Argonne, IL (United States); University of Chicago, IL (United States)

Analysis of the genes retained in the minimized Mycoplasma JCVI-Syn3A genome established that systems that repair or preempt metabolite damage are essential to life. Several genes known to have such functions were identified and experimentally validated, including 5-formyltetrahydrofolate cycloligase, coenzyme A (CoA) disulfide reductase, and certain hydrolases. Furthermore, we discovered that an enigmatic YqeK hydrolase domain fused to NadD has a novel proofreading function in NAD synthesis and could double as a MutT-like sanitizing enzyme for the nucleotide pool. Finally, we combined metabolomics and cheminformatics approaches to extend the core metabolic map of JCVI-Syn3A to include promiscuous enzymatic reactions and spontaneous side reactions. This extension revealed that several key metabolite damage control systems remain to be identified in JCVI-Syn3A, such as that for methylglyoxal.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: J. Craig Venter Institute (JCVI); National Science Foundation (NSF)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1889733

Journal Information:: mBio (Online), Journal Name: mBio (Online) Journal Issue: 4 Vol. 13; ISSN 2150-7511

Publisher:: American Society for Microbiology (ASM)Copyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
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metabolite repair
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minimal genome

Title: Metabolite Damage and Damage Control in a Minimal Genome

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